Zwitterionic hydrogel microspheres for efficient expansion and stemness maintenance of mesenchymal stem cells

In this study, we engineered dual-network amphiphilic ionic hydrogel microspheres as microcarriers for culturing in mesenchymal stem cells (MSCs), enhancing stemness retention and proliferation. The microspheres were termed DCsa. We innovatively integrated the zwitterionic sulfobetaine methacrylate (SBMA) into the DCsa microsphere structure, and with its outstanding superhydrophilic properties, formed high-energy hydration barrier sites with strong electrical neutrality on the surface of the microspheres. These sites can efficiently block the adsorption of non-specific proteins, ensuring the maintenance of stemness in long-term cultured MSCs. In addition, the addition of AAm endows the surface of microspheres with abundant functional site groups, which exhibit significant promoting effects on cell adhesion and proliferation processes. Functional assessments confirmed that MSCs cultured on DCsa maintained high cells viability and stemness over extended periods. These findings underscore the potential of DCsa microspheres as an effective three-dimensional (3D) culture platform for the large-scale propagation of MSCs, offering significant implications for the advancement of regenerative medicine and cell therapy.